Numerical analysis of geosynthetics and engineering fill in performance of reconditioned ballasted track

Over the past few decades, geosynthetics have been used extensively during track reconditioning to improve soil stability as they offer many advantages including cost effectiveness, ease of installation and minimal earthworks. Among the wide range of products in the market, geogrid remains the most commonly used geosynthetics for soil reinforcement. The aims of this paper are to investigate the effect of varying subgrade properties on track performance and to examine the effectiveness of geogrids and engineering fill for track reconditioning purposes. In the current study, numerical analyses were conducted using engineering software OptumG2, a finite element program for geotechnical stability and deformation analysis. The results of the parametric study indicated that geogrid inclusion within track substructure has considerable effect on settlement reduction and, in particular, increases the bearing capacity of railway track. The results also suggested that increase in axial stiffness of geogrids has minimal impact on track deformation. The most effective and practical location for geogrid reinforcement was achieved at interface between ballast and capping layers irrespective of the subgrade strength and stiffness. Sensitivity analyses showed that both total settlement and the bearing capacity of the railway track were most affected by the changes in the friction angle of subgrade, compared with cohesion and elastic modulus of subgrade, with or without geogrid reinforcement. The findings concluded that proper design of geogrid reinforcement can eliminate the need for or significantly reduce the thickness of engineering fill for ground improvement purposes

A performance evaluation of pruning effects on hybrid neural network

In this paper, we explore the pruning effects on a hybrid mode sequential learning algorithmnamely FuzzyARTMAP-prunable Radial Basis Function (FAM-PRBF) that utilizes FuzzyARTMAP to learn a training dataset and Radial Basis Function Network (RBFN) to performregression and classification. The pruning algorithm is used to optimize the hidden layer ofthe RBFN. The experimental results show that FAM-PRBF has successfully reduced thecomplexity and computation time of the neural network.Keywords: pruning; radial basis function network; fuzzy ARTMAP

Is there a role for remote ischemic conditioning in preventing 5-fluorouracil-induced coronary vasospasm?

Cardiac ischemia associated with chemotherapy has been linked to several anti-neoplastic agents and is multifactorial in etiology. Coronary artery vasospasm is one of the most commonly reported effects of cancer therapy that can lead to myocardial ischemia or infarction. The chemotherapy agent 5-fluorouracil (5-FU) or its oral pro-drug capecitabine can result in coronary vascular endothelial dysfunction causing coronary artery spasm, and possibly coronary thrombosis. These drugs have also been shown to be associated with myocardial infarction, malignant ventricular arrhythmias, heart failure, cardiogenic shock, and sudden death. The proposed mechanisms underlying cardiotoxicity induced by 5-FU are vascular endothelial damage followed by thrombus formation, ischemia secondary to coronary artery vasospasm, direct toxicity on myocardium, and thrombogenicity. There remains a pressing need to discover novel and effective therapies that can prevent or ameliorate 5-FU associated cardiotoxicity. To this point, promising overlap has been observed between proposed remote ischemic conditioning (RIC) cardioprotective mechanisms and 5FU-associated cardiotoxic cellular pathways. RIC, in which transient episodes of limb ischemia and reperfusion (induced by inflations and deflations of a pneumatic cuff placed on the upper arm or thigh), confer both cardioprotective and vasculoprotective effects, and may therefore prevent 5-FU coronary artery spasm/cardiotoxicity. In this review, we will be discussing the following potentially therapeutic aspects of RIC in ameliorating 5-FU associated cardiotoxicity: sequential phases of 5-FU cardiotoxicity as possible targets for dual windows of cardioprotection characteristic of RIC; protective effects of RIC on endothelial function and microvasculature in relation to 5-FU induced endothelial dysfunction/microvascular dysfunction; reduction in platelet activation by RIC in the context of 5-FU induced thrombogenicity; and the utility of improvement in mitochondrial function conferred by RIC in 5-FU induced cellular toxicity secondary to mitochondrial dysfunction

Outbreak of acute hepatitis C following the use of anti-hepatitis C virus--screened intravenous immunoglobulin therapy

BACKGROUND and AIMS: Hepatitis C virus (HCV) infection has been associated with intravenous (IV) immunoglobulin (Ig), and plasma donations used to prepare IV Ig are now screened to prevent transmission. Thirty-six patients from the United Kingdom received infusions from a batch of anti-HCV antibody-screened intravenous Ig (Gammagard; Baxter Healthcare Ltd., Thetford, Norfolk, England) that was associated with reports of acute hepatitis C outbreak in Europe. The aim of this study was to document the epidemiology of this outbreak. METHODS: Forty-six patients from the United Kingdom treated with Gammagard (34 exposed and 12 unexposed to the batch) returned epidemiological questionnaires. RESULTS: Eighty-two percent of the exposed patients (28 of 34) became positive for HCV RNA. Eighteen percent of the patients (6 of 34) who had infusions with this batch tested negative for HCV RNA, but 2 of the patients had abnormal liver function and subsequently seroconverted to anti-HCV antibody positive. Twenty-seven percent of the patients (9 of 34) developed jaundice, and 79% (27 of 34) had abnormal liver transferase levels. Virus isolates (n=21), including an isolate from the implicated batch, were genotype 1a and virtually identical by sequence analysis of the NS5 region, consistent with transmission from a single source. CONCLUSIONS: Hepatitis C infection can be transmitted by anti-HCV-screened IV Ig. Careful documentation of IV Ig batch numbers and regular biochemical monitoring is recommended for all IV Ig recipients

New insights provided by myofibril mechanics in inherited cardiomyopathies

Cardiomyopathies represent a heterogeneous group of cardiac disorders that perturb cardiac contraction and/or relaxation, and can result in arrhythmias, heart failure, and sudden cardiac death. Based on morphological and functional differences, cardiomyopathies have been classified into hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM). It has been well documented that mutations in genes encoding sarcomeric proteins are associated with the onset of inherited cardiomyopathies. However, correlating patient genotype to the clinical phenotype has been challenging because of the complex genetic backgrounds, environmental influences, and lifestyles of individuals. Thus, “scaling down” the focus to the basic contractile unit of heart muscle using isolated single myofibril function techniques is of great importance and may be used to understand the molecular basis of disease-causing sarcomeric mutations. Single myofibril bundles harvested from diseased human or experimental animal hearts, as well as cultured adult cardiomyocytes or human cardiomyocytes derived from induced pluripotent stem cells, can be used, thereby providing an ideal multi-level, cross-species platform to dissect sarcomeric function in cardiomyopathies. Here, we will review the myofibril function technique, and discuss alterations in myofibril mechanics, which are known to occur in sarcomeric genetic mutations linked to inherited HCM, DCM, and RCM, and describe the therapeutic potential for future target identification